SELENOPROTEIN EXPRESSION AND BRAIN-DEVELOPMENT IN PREWEANLING SELENIUM-DEFICIENT AND IODINE-DEFICIENT RATS

Selenium deficiency causes further impairment of thyroid hormone metab olism in iodine-deficient rats and therefore could have a role in the aetiology of both myxoedematous and neurological cretinism in humans. Thyroidal type I iodothyronine deiodinase (ID-I), cytosolic glutathion e peroxidase and phospholipid hydroperoxide glutathione peroxidase act ivities were increased in iodine-deficient adult rats and their offspr ing at 11 days of age. Thyroidal ID-I activity was unchanged and thyro idal cytosolic glutathione peroxidase activity was decreased by more t han 75% by combined selenium and iodine deficiency in 11-day-old rats, indicating that, while the thyroid retained an ability to produce 3,3 ',5-triiodothyronine (T-3), the gland was probably more susceptible to peroxidative damage caused by increased hydrogen peroxide concentrati ons driven by increased thyrotrophin. Thyroidal atrophy, common in myx oedematous cretinism, did not occur in iodine-or selenium and iodine-d eficient rat pups. Iodine deficiency increased brain type II iodothyro nine deiodinase activity 1.5-fold in 4-day-old rats and 3-fold in 11-d ay-old rats, regardless of selenium status. Thus rats were able to act ivate compensatory mechanisms in brain that would maintain T-3 concent rations in selenium and iodine deficiencies. Surprisingly, however, se lenium deficiency had a greater effect than iodine deficiency on marke rs of brain development in rat pups. Expression of the brain-derived n eurotrophic factor (BDNF) nRNA was decreased in selenium deficiency in 4- and 11-day-old pups and in combined selenium and iodine deficiency in 4-day-old pups. Iodine deficiency caused an increase in BDNF expre ssion in 11-day-old pups but had no effect on 4-day-old pups. Myelin b asic protein mRNA expression in brain was decreased by combined seleni um and iodine deficiency in 11-day-old rats.